Derivatization and Modification of Chemical Warfare Agents and Their Related Compounds for LC‐MS‐Based Analytical Applications

Abstract

The development of novel analytical methods to detect and identify chemical warfare agents (CWAs), their degradation products, metabolites, and precursors is of high importance as terrorist groups and radical regimes use or plan to use chemical weapons against civilians or military targets. Gas chromatography (GC) and liquid chromatography (LC), usually hyphenated with mass spectrometry (MS), are the major techniques used to detect and identify chemicals of concern according to the chemical convention. In this mini‐review, we describe the present state of research on the derivatization and modification of CWAs and related compounds for LC‐MS and atmospheric pressure ionization (API)‐based analysis reported in the open literature during the last 15 years. The more polar, reactive, or highly volatile agents are derivatized to expedite chromatography and to impart properties valuable for sensitive detection and identification by MS. In this article, we focus on trace analysis of CWAs, mostly G‐type nerve agents, blister agents (sulfur mustard (HD)), and the most famous blood agent, cyanide. Analytical applications are mainly in environmental matrices but also in biomedical matrices that support the investigation of CWAs use and monitoring of possible exposure to CWAs.

A novel approach for the detection and identification of sulfur mustard using liquid chromatography–electrospray ionization–tandem mass spectrometry based on its selective oxidation to sulfur mustard monoxide with N‐iodosuccinimide

“…Recently, a summary of all the derivatization studies reported in the literature for the benefit of the LC-MS analysis of chemical warfare agents in the last 15 years was reported by Weissberg et al 30 There is only one report for determining HD in the environment by LC-MS/MS using chemical derivatization in acetonitrile with potassium thioacetate (PTA), which substitutes chloride groups. 31 In general, the replacement of the chloride groups of HD with nucleophilic high ionized groups would be a good concept and has the potential to sensitively detect HD via LC-ESI-MS/MS; however, this derivatization approach cannot reveal the identity of reactive electrophile groups, such as bromide, chloride, or vinyl, which existed prior to the derivatization step.…”

“…Recently, a summary of all the derivatization studies reported in the literature for the benefit of the LC‐MS analysis of chemical warfare agents in the last 15 years was reported by Weissberg et al 30 There is only one report for determining HD in the environment by LC‐MS/MS using chemical derivatization in acetonitrile with potassium thioacetate (PTA), which substitutes chloride groups 31 …”

Oxidative derivatization of V‐type nerve agents as a tool for their structural elucidation by liquid chromatography/tandem mass spectrometry

“…To verify suspected instances of noncompliance with the treaty, analytical methods that permit the unambiguous identification of chemical warfare agents are required. Gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry (MS) are the most widely used techniques for their detection and identification 3,4 . In contrast to the mass spectra of G‐type nerve agents which display informative fragment ions, making their identification straightforward, the identification of V‐type nerve agents is more challenging, due to the existence of structural variations, including isobaric species; in addition, their spectra obtained by electron ionization mass spectrometry (EI‐MS) and electrospray ionization tandem mass spectrometry (ESI‐MS/MS) are dominated by fragments/ions originating mostly from the N,N ‐dialkylaminoethyl moiety; therefore, these agents present MS‐spectral similarity.…”

Structural elucidation of V‐type nerve agents by liquid chromatography/electrospray ionization mass spectrometry

“…Gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry (MS) are the most widely used techniques for the discrimination of these compounds, and they are routinely used for their detection and identification. 5 In contrast to G-nerve agents, which present unique structures and fragment ion masses, making their identification straightforward, when analyzing V-nerve agents, structural variations exist, including isobaric species, making their identification more challenging. A few studies have highlighted the utility of MS techniques for the differentiation and identification of V-type nerve agents.…”

“…Their mass spectra are dominated by ions originating from the N , N ‐dialkylaminoethyl moiety, and therefore, these agents present highly similar MS spectra. Gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry (MS) are the most widely used techniques for the discrimination of these compounds, and they are routinely used for their detection and identification 5 . In contrast to G‐nerve agents, which present unique structures and fragment ion masses, making their identification straightforward, when analyzing V‐nerve agents, structural variations exist, including isobaric species, making their identification more challenging.…”